Naturally occurring point mutation Cys460Trp located in the I-EGF1 domain of integrin β3 alters the binding of some anti-HPA-1a antibodies.
TRANSFUSION(2020)
Abstract
Background Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is caused by the destruction of platelets in the fetus or newborn by maternal platelet alloantibodies, mostly against human platelet antigen (HPA)-1a. Recent studies indicate that two anti-HPA subtypes exist: Type I reacts with epitopes residing on the plexin-semaphorin-integrin (PSI) and type II with plexin-semaphorin-integrin/integrin epidermal growth factor 1 (I-EGF1) domains of the beta 3 integrin. Here, we evaluated whether a Cys460Trp mutation in the I-EGF1 domain found in a patient with Glanzmann thrombasthenia can alter the binding of anti-HPA-1a. Methods Stable HEK293 cell lines expressing wild-type and mutant alpha IIb beta 3 and alpha v beta 3 were generated to prove the reactivity of different antibodies against HPA-1a. Results Flow cytometry analysis of wild-type (Cys460) and mutant (Trp460) expressed on HEK293 cells showed equal surface expression of alpha IIb beta 3 and alpha v beta 3. When tested with mutant alpha IIb beta 3 cells, reduced binding was observed in Type II but not in Type I anti-HPA-1a. These results could be confirmed with platelets carrying Cys460Trp mutation. Interestingly, reduced binding of Type I antibodies was detected with mutant alpha v beta 3 cells. Both antibody types were found in maternal sera from FNAIT cases by an antigen-capture assay with use of HEK293 transfected cells. Conclusions These observations confirm the existence of Type I and Type II anti-HPA-1a. Furthermore, this study underlines different immunogenicity of HPA-1a antigen(s) residing on either alpha IIb beta 3 or alpha v beta 3. Further analysis of FNAIT cases from mothers having a fetus with and without intracranial bleedings with use of such an approach may highlight the functional relevance of different anti-HPA-1a subtypes.
MoreTranslated text
Key words
integrin β3 alters,point mutation<scp>cys460trp</scp>located,some<scp>anti‐hpa</scp>‐<scp>1a</scp>antibodies
AI Read Science
Must-Reading Tree
Example
Generate MRT to find the research sequence of this paper
Chat Paper
Summary is being generated by the instructions you defined